1. P. Singh 1, A. Necchi 2, P. Giannatempo 2, G. Niegisch 3, G. di Lorenzo 4, C. Hsu 1, G. Sonpavde 5 University of Arizona Cancer Center 1, Tucson; Fondazione IRCCS Istituto Nazionale dei Tumori 2,Milano,Italy; Heinrich-Heine- Universität 3, Düsseldorf; Università Federico II 4, Napoli, Italy; UAB cancer center 5, Birmigham. Conclusions: This retrospective clinical experience in UC with CrCl <60 ml/min and mostly ECOG-PS 0-1 suggests that cisplatin – based chemotherapy is feasible and warrants exploration given CRs induced in metastatic disease. Incorporation of prophylactic growth factors and modified schedules may mitigate myelosuppression. RESULTS REFERENCES Methods: Data were requested and retrospectively collected from 5 collaborating institutions. All patients had stage 2 or higher UC and CrCl < 60. Patient characteristics including age, sex, indication for chemotherapy (neoadjuvant, adjuvant or metastatic disease), schedule, total dose of cisplatin, adverse effects, renal function, blood cell counts and radiologic tumor response were collected. Descriptive statistics were employed with no baseline assumptions. Hussain, S.A., et al., A study of split-dose cisplatin-based neo- adjuvant chemotherapy in muscle-invasive bladder cancer. Oncol Lett, 2012. 3(4): p. 855-859. Galsky, M.D., et al., A consensus definition of patients with metastatic urothelial carcinoma who are unfit for cisplatin-based chemotherapy. Lancet Oncol, 2011. 12(3): p. 211-4. Sonpavde, G., et al., Cisplatin-Ineligible and Chemotherapy- Ineligible Patients Should Be the Focus of New Drug Development in Patients With Advanced Bladder Cancer. Clin Genitourin Cancer, 2013. Hussain, S.A., et al., A phase I/II study of gemcitabine and fractionated cisplatin in an outpatient setting using a 21-day schedule in patients with advanced and metastatic bladder cancer. Br J Cancer, 2004. 91(5): p. 844-9. - Results: Mean total dose of cisplatin used in all patients was 414.32±198.01 mg, with 81.7% (n=85) patients receiving ≥70mg/m 2 dose per cycle. Percentage of patients with any toxicity with baseline CrCl 45 were 43.5% and 39.5%, respectively (p=0.81). Neutropenic infection occurred in 16.3% and thrombocytopenic bleed in 8.6%. Grade 3 renal toxicity was seen in only one patient (0.96%) and no toxic deaths were reported. Safety of cisplatin in patients with urothelial carcinoma (UC) and renal dysfunction Background: Patients (pts) with UC and creatinine clearance (CrCl) < 60 ml/min are considered cisplatin-ineligible. Since the safety of cisplatin use in patients with CrCl < 60 has not been comprehensively studied, we conducted a retrospective study in this population VariableMean ± SDRange Total number of patients103 Age63.72±8.0641~77 Cr Cl (CG formula)50.78±7.9726~59 Dose ≥70 mg/m 2 85 (81.73%) ECOG Performance Status (PS) 074 (71.84%) 121 (20.39%) 28 (7.77)% ToxicityN (%) Any Toxicity42 (40.38%) CrClState<= 45 (N=23) 10 (43.48%) CrClState >45 (N=81) ToxicityN (%) Any Toxicity42 (40.38%) CrClState<=45 (N=23)10 (43.48%) CrClState >45 (N=81)32 (39.51%) p-value a 0.81 Neutropenicfever17 (16.35%) ECOG 0 (N=74)11 (14.86%) ECOG 1-2 (N=29)6 (20.69%) p-value0.56 CrClState<=45 (N=23)0 (0.0%) CrClState>45 (N=81)17 (20.99%) p-value0.02 Thrombocytopenic bleed9 (8.65%) CrClState<=45 (N=23)3 (13.04%) CrClState>45 (N=81)6 (7.41%) p-value0.41 Renal toxicity None95 (91.35%) Grade 16 (5.77%) Grade 22 (1.92%) Grade 31 (0.96%) Renal Toxicity (any grade) CrClState<=45 (N=23)1 (4.35%) CrClState>45 (N=81)8 (9.88%) p-value0.68 ECOG 0 (N=74)7 (9.46%) p-value a ECOG 1-2 (N=29)2 (6.9%) Neutropenic fever p-value1.00 ECOG 0 (N=74) Neuropathy ECOG 1-2 (N=29) None91 (87.50%) p-value Grade 110 (9.62%) CrClState<= 45 (N=23) Grade 23 (2.88%) CrClState>45 (N=81) Neuropathy (Grade 2) p-value CrClState<=45 (N=23)1 (4.35%) Thrombocyt openic bleed CrClState>45 (N=81)2 (2.47%) CrCl State<=45 (N=23) p-value0.53 CrCl State>45 (N=81) Best Responses (N=42 b ) p-value PR17 (40.48%) Renal toxicity CR3 (7.14%) None SD6 (14.29%) Grade 1 PD12 (28.57%) Grade 2 Not available4 (9.52%) Grade 3 Removed from study16 (15.38%) ToxicityN (%) Any Toxicity42 (40.38%) CrCl ≤45 (N=23)10 (43.48%) CrCl >45 (N=81)32 (39.51%) p-value a 0.81 Neutropenic fever17 (16.35%) ECOG 0 (N=74)11 (14.86%) ECOG 1-2 (N=29)6 (20.69%) p-value0.56 CrCl ≤ 45 (N=23)0 (0.0%) CrCl >45 (N=81)17 (20.99%) p-value0.02 Thrombocytopenic bleed 9 (8.65%) CrCl State<=45 (N=23)3 (13.04%) CrCl State>45 (N=81)6 (7.41%) p-value0.41 Renal toxicity None95 (91.35%) Grade 16 (5.77%) Grade 22 (1.92%) Grade 31 (0.96%) Renal Toxicity (any grade) CrCl ≤45 (N=23)1 (4.35%) CrCl >45 (N=81)8 (9.88%) p-value0.68 ECOG PS 0 (N=74)7 (9.46%) ECOG 1-2 (N=29)2 (6.9%) p-value1.00 Neuropathy None91 (87.50%) Grade 110 (9.62%) Grade 23 (2.88%) Neuropathy (Grade 2) CrCl ≤45 (N=23)1 (4.35%) CrCl >45 (N=81)2 (2.47%) p-value0.53 Best Responses (N=42) PR17 (40.48%) CR3 (7.14%) SD6 (14.29%) PD12 (28.57%) Not available4 (9.52%) Removed from study16 (15.38%)